Biodegradable polymers such as polylacticor polyglycolic acid when conjugated with polyethylene glycol find wide
applications as material for nanoparticles due to their self association in aqueous milieu. Self assembly restricts these
polymers to spending their surface for intermolecular contacts and allows only one or a few covalent attachments on the
interface to bulk solvent. In contrast, biopolymers composed of units with pendant functional groups can use multiple
attachments to obtain highly reactive nanobrushes. Such a particularly useful biopolymer is poly(β-L-malic acid), which can be
obtained in high purity from biological sources. Among these covalently attached functional groups are antibodies, antisense
oligonucleotides and/or chemotherapeutic prodrugs, membrane destabilizing peptides, protecting polyethylene glycol,
gadolinium MRI contrast agent and fluorophores for imaging. While being biodegradable and nontoxic, these nano conjugates
have demonstrated high efficacy in the treatment of brain and breast cancer and proven as powerful MRI contrast agents for
the diagnosis of primary and metastatic brain tumors in preclinical animal models. Because antibodies obscure the nanobrush
character, we replace them by affinity peptides. These polymalic acid-based nanobrushes are expected to have, among other
advantages, reduced manufacturing costs, increased loading capacity increased shelf stability, superior penetration efficacy into
deep tumor tissue, reduced immunogenicity. We have succeeded in the design of such nanobrushes using public referenced
receptor-specific affinity peptides. The brake through was finding appropriate linkers for optimal geometric arrangements.
Emerging results obtained by in vivo imaging demonstrated excellent tumor specificity identifying human HER2-positive
breast cancer orsolid brain tumor.

Biography

Eggehard Holler has received his PhD in Germany 1967 in Chemistry and his Venia Legendi 1974 in Biochemistry. After ground breaking research in enzymology
and pharmacology, he joined 2008 the emerging Nanodrug Research Center at Cedars-Sinai Medical Center, Los Angeles, California, and introduced polymalic
acid as a biodegradable and versatile platform for drug delivery.